高迁移率族蛋白B1在急性坏死性胰腺炎肝损伤中的作用  

Effects of high mobility group box- 1 protein on hepatic dysfunction during murine acute necrotizing pancrealitis

作　　者：栾正刚[1] 张成[1] 马晓春[1] 郭仁宣[2] 

机构地区：[1]中国医科大学附属第一医院重症医学科,沈阳110001 [2]中国医科大学附属第一医院普通外科,沈阳110001

出　　处：《中华急诊医学杂志》2008年第10期1031-1034,共4页Chinese Journal of Emergency Medicine

摘　　要：目的探讨丙酮酸乙酯（ethyl pyruvate，EP）对大鼠急性坏死性胰腺炎（acute necrotizing pancreatitis，ANP）肝组织中高迁移率族蛋白B1（high mobility group box-1 protein，HMGB1）表达的影响。方法逆行胰胆管注射5％牛磺胆酸钠制作ANP模型。24只雄性Wistar大鼠随机分为3组（每组3只）：A组为ANP组；B组为EP组；C组为假手术组。测定血淀粉酶（amylase，AMY）和血浆ASF、肿水平变化，测定肝组织中髓过氧化物酶（myeloperoxidase，MPO）含量，RT-PCR检测肝组织HMGB1 mRNA表达，光学显微镜观察胰腺与肝组织病理变化及免疫组织化学法观察肝组织HMGB1蛋白表达。SPSS10．0统计分析软件对数据进行处理，采用单因素方差分析和q检验，以P〈0．05为差异具有统计学意义。结果A、B组血浆AMY、AST、ALT水平明显升高，但B组较A组显著下降（P〈0．05）；与C组比较，A组肝组织中MPO明显升高（P〈0．01），B组肝组织中MPO升高幅度较小。B组较A组胰腺与肝组织病理损伤明显减轻。A组大鼠肝组织HMGB1 mRNA表达较C组明显增加[A组（0．73±0．06），C组（0．28±0．04），P〈0．01]，B组其水平较A组显著降低[B组（0．46±0．05），A组（0．73±0．06），P〈0．05]。A组HMGB1明显表达于大鼠肝细胞和枯否细胞核和胞浆中，B组HMGB1表达较A组显著减弱。结论ANP时，HMGB1作为晚期炎症介质，参与了肝损伤的病理生理过程。丙酮酸乙酯能显著抑制HMGB1的表达，对ANP肝损伤有明显保护作用。Objective To explore the effects of ethyl pyruvate （EP） on hepatic high mobility group box-1 protein （HMGB1） expression in experimental routine with acute necrotizing pancreatitis （ANP）. Method ANP model was induced by retrograde injection of 5% sodium taurocholate into pancreatic duct. Twenty-four male wistar rats were divided randomly into 3 groups（ 8 rats in each group） ： group A （ ANP group） ; group B （ ANP rats reeeived ethyl pyruvate therapy） and group C （control group with sham operation）. The concentration of plasma amylase （AMY）, AST and ALT, and the activity of myeloperoxidase （MPO） in the liver were determined. The expression of HMGB1 mRNA in liver was detected by using reverse transcription polymerase chain reaction （ RTPCR）. The changes of morphological damage were observed under microscopy. The expression of HMGB1 in the liver was observed by using SP immunohistochemistry. ANOVA was perfomed with SPSS 10.0 statistical analysis software and the difference was accepted as significant if the P 〈 0.05, as verified by using Duncan＇ s and Tukey＇ s post hoe test. Results Compared with group A, levels of plasma AMY, AST and ALT in group B were markedly lower （P 〈 0.05）. Compared with group C, MPO in group A was higher significantly （P 〈 0.01）. Compared with group A, the pathological changes of pancreas and liver in group B were milder. Compared with group C, the hepatic HMGB1 mRNA expression was markedly higher in group A [ （0.28 ± 0.04） vs. （0.73 ± 0.06）, P 〈 0.01]. By contrast,the HMGB1 mRNA expression was markedly lower in group B compared with group A [（0.46± 0.05） vs. （0.73 ± 0.06）, P 〈 0. 05）. The HMGB1 protein expression in hepatocytes and Kupffer＇ s cells of rats with ANP was significantly up-regulated compared with control group, but it was reduced significantly in EP treatment group. Conclusions HMGBI as a late mediator in liver might be involved in the pathogenesis of acute hepatic injury with ANP. EP could do

关 键 词：急性坏死性胰腺炎 肝损伤 高迁移率族蛋白B1 丙酮酸乙酯 

分 类 号：R576[医药卫生—消化系统] R575[医药卫生—内科学]